Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis

Caroline E Dale; Ghazaleh Fatemifar; Tom M Palmer; Jon White; David Prieto-Merino; Delilah Zabaneh; Jorgen E L Engmann; Tina Shah; Andrew Wong; Helen R Warren; Stela McLachlan; Stella Trompet; Max Moldovan; Richard W Morris; Reecha Sofat; Meena Kumari; Elina Hyppönen; Barbara J Jefferis; Tom Gaunt; Yoav Ben-Shlomo; Ang Zhou; Aleksandra Gentry-Maharaj; Andy Ryan; UCLEB Consortium; METASTROKE consortium; Renée de Mutsert; Raymond Noordam; Mark J Caulfield; J Wouter Jukema; Bradford Worrall; Patricia B Munroe; Usha Menon; Chris Power; Diana J L Kuh; Debbie A Lawlor; Steve E Humphries; Dennis O Mook-Kanamori; George Davey Smith; Naveed Sattar; Mika J Kivimaki; Jacqueline F Price; Frank Dudridge; Aroon Hingorani; Michael V Holmes; Juan P Cass

doi:10.1161/CIRCULATIONAHA.116.026560

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis

Caroline E Dale, Ghazaleh Fatemifar, Tom M Palmer, Jon White, David Prieto-Merino, Delilah Zabaneh, Jorgen E L Engmann, Tina Shah, Andrew Wong, Helen R Warren, Stela McLachlan, Stella Trompet, Max Moldovan, Richard W Morris, Reecha Sofat, Meena Kumari, Elina Hyppönen, Barbara J Jefferis, Tom Gaunt, Yoav Ben-ShlomoAng Zhou, Aleksandra Gentry-Maharaj, Andy Ryan, UCLEB Consortium, METASTROKE consortium, Renée de Mutsert, Raymond Noordam, Mark J Caulfield, J Wouter Jukema, Bradford Worrall, Patricia B Munroe, Usha Menon, Chris Power, Diana J L Kuh, Debbie A Lawlor, Steve E Humphries, Dennis O Mook-Kanamori, George Davey Smith, Naveed Sattar, Mika J Kivimaki, Jacqueline F Price, Frank Dudridge, Aroon Hingorani, Michael V Holmes, Juan P Cass

Research output: Contribution to journal › Article (Academic Journal) › peer-review

266 Citations (Scopus)

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Abstract

Background: Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease.

Methods: 97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia. Primary outcomes were CHD, T2D, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits.

Results: Each one standard deviation (SD) higher WHRadjBMI (1SD~0.08 units) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD: 1.48; 95%CI: 1.28-1.71), similar to findings for BMI (1SD~4.6kg/m2; OR for CHD: 1.36; 95%CI: 1.22-1.52). Only WHRadjBMI increased risk of ischaemic stroke (OR 1.32; 95%CI 1.03-1.70). For T2D we find OR 1.82 (95%CI 1.38-2.42) per 1SD WHRadjBMI and OR 1.98 (95%CI 1.41-2.78) per 1SD BMI. Both WHRadjBMI and BMI were associated with increased left ventricular hypertrophy, glycaemic traits, interleukin-6, and circulating lipids. WHRadjBMI was associated with carotid intima-media thickness (37%; 95%CI: 7%-74% per 1SD).

Conclusions: Both general and central adiposity have causal effects on CHD and T2D. Central adiposity may have a stronger effect on stroke risk. Future estimates of adiposity burden on health should include measures of central and general adiposity.

Original language	English
Pages (from-to)	2373-2388
Number of pages	16
Journal	Circulation
Volume	135
Issue number	24
Early online date	12 May 2017
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.116.026560
Publication status	Published - 13 Jun 2017

Research Groups and Themes

Bristol Population Health Science Institute

Keywords

adiposity
body fat distribution
body mass index
coronary artery disease
Mendelian randomization analysis
stroke
waist-hip ratio

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/CIRCULATIONAHA.116.026560

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NIHR BRC Translational Population Health
Davey Smith, G. (Principal Investigator)
1/04/17 → 31/03/22
Project: Research, Parent
MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
IEU Theme 2
Flach, P. A. (Principal Investigator), Gaunt, T. R. (Principal Investigator) & Gaunt, T. R. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research

Professor Yoav Ben-Shlomo
- Y.Ben-Shlomobristol.acuk
- Bristol Medical School (PHS) - Professor of Clinical Epidemiology
- Bristol Poverty Institute
- Bristol Population Health Science Institute
- Cancer
- Bristol Neuroscience
- Centre for Academic Primary Care
Person: Academic , Member
Dr Tom M Palmer
- tom.palmerbristol.acuk
- eptmpbristol.acuk
- Bristol Medical School (PHS) - Senior Lecturer in Biostatistics Applied to Genetics
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Cite this

Dale, C. E., Fatemifar, G., Palmer, T. M., White, J., Prieto-Merino, D., Zabaneh, D., Engmann, J. E. L., Shah, T., Wong, A., Warren, H. R., McLachlan, S., Trompet, S., Moldovan, M., Morris, R. W., Sofat, R., Kumari, M., Hyppönen, E., Jefferis, B. J., Gaunt, T., ... Cass, J. P. (2017). Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis. Circulation, 135(24), 2373-2388. https://doi.org/10.1161/CIRCULATIONAHA.116.026560

@article{ac3c309e64c34fc1b9eff593d378f57e,

title = "Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis",

abstract = "Background: Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease. Methods: 97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia. Primary outcomes were CHD, T2D, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Results: Each one standard deviation (SD) higher WHRadjBMI (1SD~0.08 units) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD: 1.48; 95%CI: 1.28-1.71), similar to findings for BMI (1SD~4.6kg/m2; OR for CHD: 1.36; 95%CI: 1.22-1.52). Only WHRadjBMI increased risk of ischaemic stroke (OR 1.32; 95%CI 1.03-1.70). For T2D we find OR 1.82 (95%CI 1.38-2.42) per 1SD WHRadjBMI and OR 1.98 (95%CI 1.41-2.78) per 1SD BMI. Both WHRadjBMI and BMI were associated with increased left ventricular hypertrophy, glycaemic traits, interleukin-6, and circulating lipids. WHRadjBMI was associated with carotid intima-media thickness (37%; 95%CI: 7%-74% per 1SD).Conclusions: Both general and central adiposity have causal effects on CHD and T2D. Central adiposity may have a stronger effect on stroke risk. Future estimates of adiposity burden on health should include measures of central and general adiposity.",

keywords = "adiposity, body fat distribution, body mass index, coronary artery disease, Mendelian randomization analysis, stroke, waist-hip ratio",

author = "Dale, {Caroline E} and Ghazaleh Fatemifar and Palmer, {Tom M} and Jon White and David Prieto-Merino and Delilah Zabaneh and Engmann, {Jorgen E L} and Tina Shah and Andrew Wong and Warren, {Helen R} and Stela McLachlan and Stella Trompet and Max Moldovan and Morris, {Richard W} and Reecha Sofat and Meena Kumari and Elina Hypp{\"o}nen and Jefferis, {Barbara J} and Tom Gaunt and Yoav Ben-Shlomo and Ang Zhou and Aleksandra Gentry-Maharaj and Andy Ryan and {UCLEB Consortium} and {METASTROKE consortium} and {de Mutsert}, Ren{\'e}e and Raymond Noordam and Caulfield, {Mark J} and Jukema, {J Wouter} and Bradford Worrall and Munroe, {Patricia B} and Usha Menon and Chris Power and Kuh, {Diana J L} and Lawlor, {Debbie A} and Humphries, {Steve E} and Mook-Kanamori, {Dennis O} and {Davey Smith}, George and Naveed Sattar and Kivimaki, {Mika J} and Price, {Jacqueline F} and Frank Dudridge and Aroon Hingorani and Holmes, {Michael V} and Cass, {Juan P}",

year = "2017",

month = jun,

day = "13",

doi = "10.1161/CIRCULATIONAHA.116.026560",

language = "English",

volume = "135",

pages = "2373--2388",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "24",

}

Dale, CE, Fatemifar, G, Palmer, TM, White, J, Prieto-Merino, D, Zabaneh, D, Engmann, JEL, Shah, T, Wong, A, Warren, HR, McLachlan, S, Trompet, S, Moldovan, M, Morris, RW, Sofat, R, Kumari, M, Hyppönen, E, Jefferis, BJ, Gaunt, T , Ben-Shlomo, Y, Zhou, A, Gentry-Maharaj, A, Ryan, A, UCLEB Consortium, METASTROKE consortium, de Mutsert, R, Noordam, R, Caulfield, MJ, Jukema, JW, Worrall, B, Munroe, PB, Menon, U, Power, C, Kuh, DJL, Lawlor, DA, Humphries, SE, Mook-Kanamori, DO, Davey Smith, G, Sattar, N, Kivimaki, MJ, Price, JF, Dudridge, F, Hingorani, A, Holmes, MV & Cass, JP 2017, 'Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis', Circulation, vol. 135, no. 24, pp. 2373-2388. https://doi.org/10.1161/CIRCULATIONAHA.116.026560

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis. / Dale, Caroline E; Fatemifar, Ghazaleh; Palmer, Tom M et al.
In: Circulation, Vol. 135, No. 24, 13.06.2017, p. 2373-2388.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus

T2 - A Mendelian Randomization Analysis

AU - Dale, Caroline E

AU - Fatemifar, Ghazaleh

AU - Palmer, Tom M

AU - White, Jon

AU - Prieto-Merino, David

AU - Zabaneh, Delilah

AU - Engmann, Jorgen E L

AU - Shah, Tina

AU - Wong, Andrew

AU - Warren, Helen R

AU - McLachlan, Stela

AU - Trompet, Stella

AU - Moldovan, Max

AU - Morris, Richard W

AU - Sofat, Reecha

AU - Kumari, Meena

AU - Hyppönen, Elina

AU - Jefferis, Barbara J

AU - Gaunt, Tom

AU - Ben-Shlomo, Yoav

AU - Zhou, Ang

AU - Gentry-Maharaj, Aleksandra

AU - Ryan, Andy

AU - UCLEB Consortium

AU - METASTROKE consortium

AU - de Mutsert, Renée

AU - Noordam, Raymond

AU - Caulfield, Mark J

AU - Jukema, J Wouter

AU - Worrall, Bradford

AU - Munroe, Patricia B

AU - Menon, Usha

AU - Power, Chris

AU - Kuh, Diana J L

AU - Lawlor, Debbie A

AU - Humphries, Steve E

AU - Mook-Kanamori, Dennis O

AU - Davey Smith, George

AU - Sattar, Naveed

AU - Kivimaki, Mika J

AU - Price, Jacqueline F

AU - Dudridge, Frank

AU - Hingorani, Aroon

AU - Holmes, Michael V

AU - Cass, Juan P

PY - 2017/6/13

Y1 - 2017/6/13

N2 - Background: Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease. Methods: 97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia. Primary outcomes were CHD, T2D, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Results: Each one standard deviation (SD) higher WHRadjBMI (1SD~0.08 units) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD: 1.48; 95%CI: 1.28-1.71), similar to findings for BMI (1SD~4.6kg/m2; OR for CHD: 1.36; 95%CI: 1.22-1.52). Only WHRadjBMI increased risk of ischaemic stroke (OR 1.32; 95%CI 1.03-1.70). For T2D we find OR 1.82 (95%CI 1.38-2.42) per 1SD WHRadjBMI and OR 1.98 (95%CI 1.41-2.78) per 1SD BMI. Both WHRadjBMI and BMI were associated with increased left ventricular hypertrophy, glycaemic traits, interleukin-6, and circulating lipids. WHRadjBMI was associated with carotid intima-media thickness (37%; 95%CI: 7%-74% per 1SD).Conclusions: Both general and central adiposity have causal effects on CHD and T2D. Central adiposity may have a stronger effect on stroke risk. Future estimates of adiposity burden on health should include measures of central and general adiposity.

AB - Background: Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease. Methods: 97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia. Primary outcomes were CHD, T2D, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Results: Each one standard deviation (SD) higher WHRadjBMI (1SD~0.08 units) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD: 1.48; 95%CI: 1.28-1.71), similar to findings for BMI (1SD~4.6kg/m2; OR for CHD: 1.36; 95%CI: 1.22-1.52). Only WHRadjBMI increased risk of ischaemic stroke (OR 1.32; 95%CI 1.03-1.70). For T2D we find OR 1.82 (95%CI 1.38-2.42) per 1SD WHRadjBMI and OR 1.98 (95%CI 1.41-2.78) per 1SD BMI. Both WHRadjBMI and BMI were associated with increased left ventricular hypertrophy, glycaemic traits, interleukin-6, and circulating lipids. WHRadjBMI was associated with carotid intima-media thickness (37%; 95%CI: 7%-74% per 1SD).Conclusions: Both general and central adiposity have causal effects on CHD and T2D. Central adiposity may have a stronger effect on stroke risk. Future estimates of adiposity burden on health should include measures of central and general adiposity.

KW - adiposity

KW - body fat distribution

KW - body mass index

KW - coronary artery disease

KW - Mendelian randomization analysis

KW - stroke

KW - waist-hip ratio

U2 - 10.1161/CIRCULATIONAHA.116.026560

DO - 10.1161/CIRCULATIONAHA.116.026560

M3 - Article (Academic Journal)

C2 - 28500271

SN - 0009-7322

VL - 135

SP - 2373

EP - 2388

JO - Circulation

JF - Circulation

IS - 24

ER -

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis

Abstract

Research Groups and Themes

Keywords

UN SDGs

Access to Document

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Projects

NIHR BRC Translational Population Health

MRC UoB UNITE Unit - Programme 1

IEU Theme 2

Profiles

Professor Yoav Ben-Shlomo

Dr Tom M Palmer

Cite this